Local Anesthetics for Dentistry
1 | Chemical Characteristics and Anesthetic Properties
One of the most important elements of pain management in dentistry is the capability to provide effective local anesthesia. The local anesthetic agents available today provide the practitioner multiple options to effectively manage the pain associated with dental procedures.
These agents are extremely safe and fulfill most of the characteristics of an ideal local anesthetic. They all can be administered with minimal tissue irritation, have an extremely low incidence of allergic reactions, while providing rapid onsets and adequate durations of surgical anesthesia.
The clinical characteristics of the local anesthetic agents such as onset times, potency and duration, can be attributed to differences in chemical properties of their molecular structures:
• The more an anesthetic exists in an ionized state, the slower is its onset time. This is the case of ester anesthetics in general. For example, procaine (Novacain), with a pKa of 8.9, is 98% ionized at a normal tissue pH of 7.4 and has a very slow onset.
• The lipid solubility characteristics of a local anesthetic best predict potency. Procaine is one of the least lipid soluble and least potent local anesthetics while bupivacaine is very lipid soluble and one of the most potent
• The protein binding characteristics are a primary determinant of the duration of anesthesia. Lidocaine’s short duration and bupivacaine’s long duration are due, in part, to their distinctly different protein binding characteristics.
It is thus clear that lipid solubility, ionization and protein binding properties contribute to the clinical characteristics of local anesthetics. However, factors such as the site of injection, inclusion of a vasoconstrictor, concentration and volume of the injected drug, and inherent vasodilatory properties of the anesthetic, also influence the clinical performance of a local anesthetic.
Because of their superior chemical and anesthetic properties, rarely reported allergenic reactions, and excellent safety profiles, only amide anesthetics are currently formulated into dental cartridges for injection.
Lidocaine Hydrochloride (Formulated as 2% lidocaine with 1:100,000 epinephrine and 2% lidocaine with 1:50,000 epinephrine)
Lidocaine, the first amide anesthetic, was introduced into dental practice in the 1950s and has become one of most popular dental local anesthetics in the United States. Besides having excellent anesthetic efficacy, lidocaine has limited allergenicity.
The 2% lidocaine with 1:100,000 epinephrine is considered the gold standard when evaluating the efficacy and safety of newer anesthetics. The 1:50,000 epinephrine formulation is employed for infiltration injection when additional hemostasis is required.
Mepivacaine Hydrochloride (Formulated as 3% mepivacaine plain and 2% mepivacaine 1:20,000 levonordefrin)
Mepivacaine has an important place in dental anesthesia because it has minimal vasodilating properties and can therefore provide profound local anesthesia without requiring a vasoconstrictor such as epinephrine or levonordefrin. The availability of a 3% formulation not containing a vasoconstrictor is a valuable addition to a dentist’s armamentarium.
Prilocaine Hydrochloride (Formulated as 4% prilocaine plain and 4% prilocaine with 1:200,000 epinephrine)
Similar to mepivacaine, prilocaine is not a potent vasodilator and can provide excellent oral anesthesia either with or without a vasoconstrictor. The formulation containing epinephrine has anesthetic characteristics similar to 2% lidocaine 1:100,000 epinephrine. One of prilocaine’s metabolic products (toluidine) has been associated with the development of methemoglobinemia.
Articaine Hydrochloride (Formulated as 4% articaine with 1:100,000 epinephrine and 4% articaine with 1:200,000 epinephrine)
The molecular structure of the amide local anesthetic articaine is somewhat unique, containing a thiophene (sulfur-containing) ring. Studies evaluating mandibular block and maxillary infiltration anesthesia, have generally found onset times, duration and anesthetic profundity of articaine formulations to be comparable to 2% lidocaine with 1:100,000 epinephrine.
There is a developing clinical research literature supporting articaine’s superior diffusion properties and that anesthesia may be possibly induced following buccal infiltration in the mandible.
Bupivacaine Hydrochloride (Formulated as 0.5% bupivacaine 1:200,000 epinephrine)
The long-acting amide local anesthetics bupivacaine has found an important place in dentists’ armamentarium. Bupivacaine is the only long-acting local anesthetic agent formulated in a dental cartridge. When compared to short-acting local anesthetics, bupivacaine’s prolonged soft tissue and periosteal anesthesia has been shown to limit post-operative pain. This clinical characteristic is a valuable asset in the overall management of surgical and postoperative pain associated with dental care.
Clinical trials have shown that bupivacaine, having a pKa of 8.1, has a slightly slower onset time than conventional amide anesthetics.
A combination strategy for managing postoperative pain using a nonsteroidal anti-inflammatory analgesic such as ibuprofen or naproxen, prior to or immediately following surgery in combination with a long-acting anesthetic following surgery, may limit the need for opioid analgesic.
* See the drug monograph for local anesthetic agents at the end of the chapter.
** Drugs that have Pregnancy Category Rating of “C” should be used with caution during pregnancy.
There are two local anesthetic agents used in dentistry that reportedly induce methemoglobinemia. The first agent is the topical local anesthetic benzocaine and the second agent is the injectable (and topical) local anesthetic prilocaine. The mechanism of action is that both of these anesthetics oxidize hemoglobin to methemoglobin. As the level of methemoglobin continues to increase in the blood, cyanosis develops and additional symptoms appear with the potential for progression to unconsciousness and death. This phenomena invariably occurs with excessive dose of either agent. Fortunately, methemoglobinemia treatments using methylene blue are generally effective.
Systemic Toxicity Reactions Due to Excessive Local Anesthetic
When excessive doses of any of these local anesthetics are administered, excitatory central nervous system (CNS) reactions, such as tremors, muscle twitching, shivering and clonic-tonic convulsions have been reported. These initial excitatory reactions are thought to be due to a selective blockade of small inhibitory neurons within the limbic system of the CNS. Whether this initial excitatory reaction is apparent or not, a generalized CNS depression with symptoms of sedation, drowsiness, lethargy and life-threatening respiratory depression follows if blood concentrations of the local anesthetic agent continue to rise. Severe bradycardia may also occur due to the ability of local anesthetics to block sodium channels in the heart. Compliance with local anesthetic dosing guidelines is the first and most important strategy for preventing this adverse event. Dosing calculations used to avoid systemic reactions to local anesthetics are dependent on the agent administered and the patient’s body weight (Table 2).
Toxicity Reactions Due to Excessive Vasoconstrictors
Epinephrine and levonordefrin are the two vasoconstrictors formulated with local anesthetic agents in dental cartridges. The use of a vasoconstrictor can improve the safety of the formulation by slowing the systemic absorption of the local anesthetic and decrease the peak blood levels of the anesthetic. There is minimal stimulation of the cardiovascular system following submucosal injection of one or two cartridges of anesthetic containing epinephrine or levonordefrin. However, when excessive amounts of these vasoconstrictors are administered, or when inadvertently administered intravascularly, cardiovascular stimulation, with clinically significant increases in blood pressure and heart rate, can occur. Using anesthetic formulations containing no or limited amounts of vasoconstrictors, using a slow injection technique, and aspirating carefully and repeatedly are common recommendations to prevent rapid systemic absorption of epinephrine and levonordefrin.
Although vasoconstrictors are rarely contraindicated, the potential stimulation of the cardiovascular system following intravascular injections should guide the dental practitioners to avoid vasoconstrictor-containing formulations in cardiovascularly compromised populations if possible. A common recommendation, when a vasoconstrictor is required for a dental treatment and when there is a medical history that suggests a need for caution, is to limit the dose of epinephrine to 0.04 mg (See Section 2 for information specific to children). This can be achieved by limiting the total anesthetics used to: one cartridge of an anesthetic containing 1:50,000 epinephrine, two cartridges of an anesthetic containing 1:100,000 epinephrine, or four cartridges of an anesthetic containing 1:200,000 epinephrine.
* epi = epinephrine; levo = levonordefrin
† The volume of a dental cartridge is approximated to 1.8 mL
‡ 1:100,000 epi = 0.01 mg/mL; A 1.8 mL cartridge contains 0.018 mg epi
§ Maximum Recommended Dose (MRD); 1.0 kg = 2.2 lbs; 70 kg adult = 150 lbs
¶ Maximum Recommended Dose (MRD) for epinephrine for a healthy adult is 0.2 mg. The maximum number of cartridges for an adult receiving 2% lidocaine 1:100,000 or 1:50,000 epinephrine are based on the 0.2 mg maximum for epinephrine in these formulations.
4 | Topical Anesthetics for Dentistry
Professional application of topical local anesthetics is a valuable addition to a dentist’s pain control armamentarium, providing surface anesthesia that can mitigate the discomfort of anesthetic needle insertion as well as pain from soft tissue lesions, minor gingival and periodontal procedures and possibly small biopsies. When applied in metered amounts to oral mucosa, topical anesthetics have limited absorption and reports of adverse reactions are rare and usually limited to localized allergic reactions.
spray, gel, or ointment